What is the next test to order for a 32-year-old female presenting with oligomenorrhea, fatigue, hirsutism, and unintentional weight gain, with a past medical history (PMH) of major depressive disorder (MDD) on escitalopram?

From the Guidelines

The next test to order for this patient is a comprehensive hormonal panel including serum testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, thyroid function tests (TSH, free T4), prolactin, and a fasting glucose with insulin levels. Given her presentation of oligomenorrhea, hirsutism, fatigue, and unintentional weight gain, polycystic ovary syndrome (PCOS) should be strongly suspected, but other endocrine disorders like thyroid dysfunction, hyperprolactinemia, and Cushing's syndrome need to be ruled out 1. Additionally, a pelvic ultrasound would be valuable to evaluate for polycystic ovaries. It's essential to note that her escitalopram for MDD is unlikely to cause these symptoms, though some antidepressants can contribute to weight gain. The hormonal workup will help differentiate between PCOS (characterized by elevated androgens and insulin resistance), thyroid disorders (which can cause menstrual irregularities and fatigue), and other endocrine conditions that may present similarly. Early diagnosis is crucial as these conditions can have long-term metabolic and reproductive consequences if left untreated.

Some key points to consider in the diagnosis and management of PCOS include:

• The importance of screening for cardiometabolic features, such as abdominal obesity, diabetes, dyslipidemia, and hypertension, as women with PCOS are at an increased risk for development of metabolic syndrome features 1
• The use of metformin in patients with PCOS who have cardiometabolic features such as abdominal obesity and insulin resistance 1
• The need for close monitoring of weight changes, blood pressure, fasting lipid panel, glycemic control, and assessments for CVD risk in women with PCOS 1
• The consideration of psychological factors, such as anxiety, depression, and eating disorders, which are prevalent in PCOS, and the importance of addressing lifestyle-based interventions with cultural sensitivities and weight-related stigma in mind 1

From the Research

Diagnostic Approach

The patient's symptoms of oligomenorrhea, fatigue, hirsutism, and unintentional weight gain, along with a past medical history of major depressive disorder (MDD) on escitalopram, suggest the possibility of polycystic ovary syndrome (PCOS) or Cushing's syndrome (CS).

Key Considerations

• The presence of hirsutism, menstrual irregularities, and weight gain are common in both PCOS and CS, making differential diagnosis challenging 2, 3.
• Cushing's syndrome can present with similar symptoms to PCOS, including menstrual irregularities and hyperandrogenism, and its diagnosis should be considered, especially if there are other disturbances that increase the pretest probability 3.
• The measurement of total testosterone (TT) or bioavailable testosterone (BT) levels, or the calculation of the free androgen index (FAI), may help differentiate between mild CS and PCOS, with TT levels being potentially useful in this regard 4.

Next Steps

• Given the overlap in symptoms between PCOS and CS, and the potential for CS to be missed or delayed in diagnosis, further testing is warranted to rule out CS.
• A 24-hour urine free cortisol test or a low-dose dexamethasone suppression test (LDDST) could be considered as the next step to evaluate for hypercortisolism, which is a key feature of CS 2, 3.
• Additionally, assessing the patient's LH/FSH ratio may provide further insight, although its utility may be limited in differentiating between PCOS and CS, especially in the context of obesity or normal BMI 5.
• It is crucial to approach the diagnosis systematically, considering the clinical presentation, laboratory findings, and the potential for co-existing conditions like MDD, which may influence the interpretation of symptoms and test results.

Potential Tests

• 24-hour urine free cortisol test
• Low-dose dexamethasone suppression test (LDDST)
• Total testosterone (TT) or bioavailable testosterone (BT) levels
• LH/FSH ratio
• Other tests as indicated based on clinical suspicion and initial findings, such as imaging studies to evaluate for adrenal or pituitary abnormalities in cases of suspected CS.